REG - GSK PLC - FDA accepts new drug application for gepotidacin

GSKAnnouncement

16/10/2024 07:00

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RNS Number : 2958I  GSK PLC  16 October 2024

 Issued: 16 October 2024, London UK

 

Gepotidacin accepted for priority review by US FDA for treatment of
uncomplicated urinary tract infections in female adults and adolescents

 

 * Application supported by positive results from pivotal phase III EAGLE-2 and
EAGLE-3 trials

 * 26 March 2025 assigned as action date for FDA decision

 * Gepotidacin could be the first in a new class of oral antibiotic treatment for
uUTIs in over 20 years

 

GSK plc (LSE/NYSE: GSK) today announced that the US Food and Drug
Administration (FDA) has accepted the New Drug Application (NDA) for
gepotidacin, an investigational, first-in-class oral antibiotic with a novel
mechanism of action for the treatment of female adults (³40 kg) and
adolescents (³12 years, ³40 kg) with uncomplicated urinary tract infections
(uUTIs).

 

The FDA has granted Priority Review for this application and assigned a
Prescription Drug User Fee Act (PDUFA) action date of 26 March 2025.

 

Over half of all women are affected by uUTIs in their lifetime 1  (#_edn1) ,
with approximately 30% suffering from recurrent disease which can cause
significant patient burden, including discomfort and restriction of daily
activities. 2  (#_edn2) New treatments are needed as the number of uUTIs
caused by drug-resistant bacteria is increasing and can result in higher
treatment failure rates. 3  (#_edn3) Gepotidacin is a late-stage antibiotic in
GSKÕs growing infectious disease portfolio and could be the first in a new
class of oral antibiotics for uUTIs in over 20 years.

 

The NDA is supported by positive results from the pivotal phase III EAGLE-2
and EAGLE-3 trials. In these studies, gepotidacin demonstrated non-inferiority
to nitrofurantoin, the current standard of care for uUTI, in female adults
(³40 kg) and adolescents (³12 years, ³40 kg) with a confirmed uUTI and a
uropathogen susceptible to nitrofurantoin. In EAGLE-3, gepotidacin achieved
statistically significant superiority versus nitrofurantoin, demonstrating
therapeutic success in 58.5% (162/277) of participants compared to 43.6%
(115/264) for nitrofurantoin (treatment difference 14.6%, 95% CI (6.4, 22.8)).
In EAGLE-2, gepotidacin demonstrated therapeutic success in 50.6% (162/320) of
participants compared to 47.0% (135/287) for nitrofurantoin (treatment
difference 4.3%, 95% CI (-3.6, 12.1)).

 

The safety and tolerability profile of gepotidacin in the EAGLE-2 and EAGLE-3
phase III trials was consistent with previous trials of gepotidacin. The most
commonly reported adverse events (AEs) in gepotidacin participants were
gastrointestinal (GI). Diarrhoea was the most common (16% of participants),
followed by nausea (9%). Of the participants who reported GI AEs in the
gepotidacin group, the maximum severity were mild (69% Grade 1) and moderate
(28% Grade 2). Participants with Grade 3 GI events accounted for 3% of all
patients with GI events and occurred in <1% of all participants. There was
one drug-related serious adverse event in each treatment arm (gepotidacin and
nitrofurantoin) across the two trials.

 

The development of gepotidacin has been funded in part with federal funds from
the US Department of Health and Human Services, Administration for Strategic
Preparedness and Response, Biomedical Advanced Research and Development
Authority (BARDA), under Other Transaction Agreement number HHSO100201300011C
and with federal funds awarded by the Defense Threat Reduction Agency under
agreement number HDTRA1-07-9-0002.

( )

About the EAGLE (Efficacy of Antibacterial Gepotidacin Evaluated) phase III
programme

The global phase III clinical programme for gepotidacin in adults and
adolescents consists of three trials:

 

EAGLE-2 and EAGLE-3 (non-inferiority uUTI trials) compared the efficacy and
safety of gepotidacin (1,500mg administered orally twice daily for five days)
to nitrofurantoin (100mg administered orally twice daily for five days) with
1531 and 1605 female adults and adolescents with uncomplicated urinary tract
infections, respectively. Across both trials, the duration of follow-up for
participants was approximately 28 days, and the primary endpoint was the
combined clinical and microbiological response at the Test-of-Cure (ToC) visit
(days 10-13) in patients with qualifying uropathogens susceptible to
nitrofurantoin.

 

EAGLE-1 (non-inferiority urogenital gonorrhoea trial) compared the efficacy
and safety of gepotidacin to ceftriaxone plus azithromycin in 628 patients
with uncomplicated urogenital gonorrhoea caused by Neisseria gonorrhoeae.

 

About gepotidacin

Gepotidacin, discovered by GSK scientists, is an investigational bactericidal,
first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA
replication by a distinct binding site, a novel mechanism of action and for
most pathogens, provides well-balanced inhibition of two different Type II
topoisomerase enzymes. This provides activity against most target uropathogens
(such as E. coli and S. saprophyticus), and N. gonorrhoeae, including isolates
resistant to current antibiotics. Efficacy and safety in patients have been
demonstrated in uUTI and gonorrhoea phase III clinical trials, including those
with drug-resistant pathogens. Due to the well-balanced inhibition,
gepotidacin target-specific mutations in both enzymes are needed to
significantly affect susceptibility to gepotidacin. Therefore, leading to a
lower potential for resistance development.

 

GSK in infectious diseases

GSK has pioneered innovation in infectious diseases for over 70 years, and the
CompanyÕs pipeline of medicines and vaccines is one of the largest and most
diverse in the industry, with a goal of developing preventive and therapeutic
treatments for multiple disease areas or diseases with high unmet needs
globally. GSKÕs expertise and capabilities in innovation, access and
stewardship position the Company uniquely to help prevent and mitigate the
challenge of antimicrobial resistance.

 

In antimicrobials, in addition to gepotidacin, GSK entered into an exclusive
licence agreement with Spero Therapeutics, Inc. in September 2022 to add
tebipenem HBr, a late-stage antibiotic and potential treatment for complicated
urinary tract infections (cUTIs), to the pipeline and are currently enrolling
for PIVOT-PO, a phase III trial. In March 2023, GSK announced an exclusive
licence agreement with Scynexis for Brexafemme (ibrexafungerp tablets), a
first-in-class antifungal for the treatment of vulvovaginal candidiasis (VVC)
and reduction in the incidence of recurrent VVC.

 

About GSK

GSK is a global biopharma company with a purpose to unite science, technology,
and talent to get ahead of disease together. Find out more at gsk.com.

 

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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially from those
projected. Such factors include, but are not limited to, those described under
Item 3.D ÒRisk factorsÓ in GSKÕs Annual Report on Form 20-F for 2023, and
GSKÕs Q2 Results for 2024.

 

 

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 1  (#_ednref1) Czajkowski, K., et al. Urinary tract infection in women. Prz
Menopauzalny. 2021;20(1):40-7.

 2  (#_ednref2) Little P, Merriman R, Turner S, et al. Presentation, pattern,
and natural course of severe symptoms, and role of antibiotics and antibiotic
resistance among patients presenting with suspected uncomplicated urinary
tract infection in primary care: observational study. BMJ. 2010;340:b5633.

 3  (#_ednref3) Kaye KS, et al. Antimicrobial resistance trends in urine
Escherichia coli isolates from adult and adolescent females in the United
States from 2011 to 2019: rising ESBL strains and impact on patient
management. Clin Infect Dis 2021;73:1992Ð1999. doi: 10.1093/cid/ciab560

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